title: Structure and function of voltage-gated sodium channels at atomic resolution.
abstract: Voltage-gated sodium channels initiate action potentials in nerve, muscle and other excitable cells. Early physiological studies described sodium selectivity, voltage-dependent activation and fast inactivation, and developed conceptual models for sodium channel function. This review article follows the topics of my 2013 Sharpey-Schafer Prize Lecture and gives an overview of research using a combination of biochemical, molecular biological, physiological and structural biological approaches that have elucidated the structure and function of sodium channels at the atomic level. Structural models for voltage-dependent activation, sodium selectivity and conductance, drug block and both fast and slow inactivation are discussed. A perspective for the future envisions new advances in understanding the structural basis for sodium channel function and the opportunity for structure-based discovery of novel therapeutics.
authors.affiliation: W. A. Catterall: Department of Pharmacology, Box 357280, University of Washington, Seattle, WA 98195-7280, USA. wcatt@u.washington.edu.
authors.forename: William A
authors.initials: WA
authors.lastname: Catterall
mesh_terms: D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D011487:Protein Conformation; D012964:Sodium / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D061566:Voltage-Gated Sodium Channels / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D026941:Sodium Channel Blockers; D061566:Voltage-Gated Sodium Channels; D012964:Sodium